A number of neurodegenerative diseases are associated with defects in the sequestosome gene SQSTM1 (MIM:601530), including frontotemporal dementia and/or amyotrophic lateral sclerosis 3 (FTDALS3, FBhh0001319) and neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset (NADGP, FBhh0001320). The SQSTM1 gene encodes a scaffolding protein that regulates a variety of biologic processes, including NFKB1 signaling, apoptosis, transcription regulation, and ubiquitin-mediated autophagy. There is a single fly ortholog of SQSTM1, Dmel\ref(2)P, for which classical loss-of-function mutations, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
The human SQSTM1 gene has not been introduced into flies.
Using several different drivers and RNAi reagents, knockdown of ref(2)P expression was effected in all neurons, in dopaminergic neurons, or in motor neurons; longevity and locomotor function were assessed over time. Severe progressive locomotor defects were observed in all cases; a modest but significant increase in median lifespan was also observed.
[updated Feb. 2021 by FlyBase; FBrf0222196]
The SQSTM1 gene encodes a scaffolding protein that regulates a variety of biologic processes, including NFKB1 signaling, apoptosis, transcription regulation, and ubiquitin-mediated autophagy (review by Rea et al., 2014; pubmed:24486447). [from MIM:601530; 2021.02.22]
SQSTM1 encodes a multifunctional scaffolding protein that is required for selective autophagy activation by ubiquitinated proteins; it functions as a bridge between polyubiquitinated cargo and autophagosomes. SQSTM1 may play multiple regulatory roles, including regulation of activation of the nuclear factor kappa-β signaling pathway. [Gene Cards, SQSTM1; 21.02.22]
One to one: 1 human gene to 1 Drosophila gene.
Moderate-scoring ortholog of human SQSTM1 (1 Drosophila to 1 human). Dmel\ref(2)P shares 23% identity and 33% similarity with the human gene.
